Trial Outcomes & Findings for Effects Of CP-690,550 (Tasocitinib) On Cholesterol Metabolism In Patients With Active Rheumatoid Arthritis (NCT NCT01262118)
NCT ID: NCT01262118
Last Updated: 2013-01-23
Results Overview
Blood level of HDL-C was measured following a 12-hours fasting.
COMPLETED
PHASE1
69 participants
Baseline
2013-01-23
Participant Flow
Participant milestones
| Measure |
Rheumatoid Arthritis Cohort
Active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days and then received CP-690,550 10 mg tablet orally twice daily for 6 weeks.
|
Healthy Volunteers Cohort
Healthy volunteers with similar baseline demographic characteristics as the active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days.
|
|---|---|---|
|
Baseline Assessment Period (3 Days)
STARTED
|
36
|
33
|
|
Baseline Assessment Period (3 Days)
COMPLETED
|
36
|
33
|
|
Baseline Assessment Period (3 Days)
NOT COMPLETED
|
0
|
0
|
|
Treatment Period (6 Weeks)
STARTED
|
36
|
0
|
|
Treatment Period (6 Weeks)
COMPLETED
|
36
|
0
|
|
Treatment Period (6 Weeks)
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Effects Of CP-690,550 (Tasocitinib) On Cholesterol Metabolism In Patients With Active Rheumatoid Arthritis
Baseline characteristics by cohort
| Measure |
Rheumatoid Arthritis Cohort
n=36 Participants
Active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days and then received CP-690,550 10 mg tablet orally twice daily for 6 weeks.
|
Healthy Volunteers Cohort
n=33 Participants
Healthy volunteers with similar baseline demographic characteristics as the active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days.
|
Total
n=69 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
18 to 44 years
|
9 participants
n=99 Participants
|
7 participants
n=107 Participants
|
16 participants
n=206 Participants
|
|
Age, Customized
45 to 64 years
|
25 participants
n=99 Participants
|
25 participants
n=107 Participants
|
50 participants
n=206 Participants
|
|
Age, Customized
Greater than or equal to (>=) 65 years
|
2 participants
n=99 Participants
|
1 participants
n=107 Participants
|
3 participants
n=206 Participants
|
|
Sex: Female, Male
Female
|
30 Participants
n=99 Participants
|
28 Participants
n=107 Participants
|
58 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
11 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: BaselinePopulation: Full analysis set (FAS) included all enrolled participants who had any measurement of cholesterol ester production rate available.
Blood level of HDL-C was measured following a 12-hours fasting.
Outcome measures
| Measure |
Rheumatoid Arthritis Cohort
n=36 Participants
Active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days and then received CP-690,550 10 mg tablet orally twice daily for 6 weeks.
|
Healthy Volunteer Cohort
n=31 Participants
Healthy volunteers with similar baseline demographic characteristics as the active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days.
|
|---|---|---|
|
High-density Lipoprotein Cholesterol (HDL-C) Concentration at Baseline
|
54.30 milligram per deciliter (mg/dL)
Standard Deviation 12.52
|
63.43 milligram per deciliter (mg/dL)
Standard Deviation 16.89
|
PRIMARY outcome
Timeframe: Week 6Population: FAS included all enrolled participants who had any measurement of cholesterol ester production rate available.
Blood level of HDL-C was measured following a 12-hours fasting.
Outcome measures
| Measure |
Rheumatoid Arthritis Cohort
n=36 Participants
Active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days and then received CP-690,550 10 mg tablet orally twice daily for 6 weeks.
|
Healthy Volunteer Cohort
Healthy volunteers with similar baseline demographic characteristics as the active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days.
|
|---|---|---|
|
High-density Lipoprotein Cholesterol (HDL-C) Concentration at Week 6
|
62.34 mg/dL
Standard Deviation 15.24
|
—
|
PRIMARY outcome
Timeframe: BaselinePopulation: FAS included all enrolled participants who had any measurement of cholesterol ester production rate available. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
Cholesterol ester production rate was calculated using a 3-pool model with a simulation, analysis and modeling (SAAM II) program.
Outcome measures
| Measure |
Rheumatoid Arthritis Cohort
n=34 Participants
Active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days and then received CP-690,550 10 mg tablet orally twice daily for 6 weeks.
|
Healthy Volunteer Cohort
n=31 Participants
Healthy volunteers with similar baseline demographic characteristics as the active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days.
|
|---|---|---|
|
Cholesterol Ester Production Rate at Baseline
|
1.09 (mg per kilogram) per hour ([mg/kg]/hr)
Standard Deviation 0.24
|
1.11 (mg per kilogram) per hour ([mg/kg]/hr)
Standard Deviation 0.26
|
PRIMARY outcome
Timeframe: Week 6Population: FAS included all enrolled participants who had any measurement of cholesterol ester production rate available. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
Cholesterol ester production rate was calculated using a 3-pool model with a simulation, analysis and modeling (SAAM II) program.
Outcome measures
| Measure |
Rheumatoid Arthritis Cohort
n=33 Participants
Active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days and then received CP-690,550 10 mg tablet orally twice daily for 6 weeks.
|
Healthy Volunteer Cohort
Healthy volunteers with similar baseline demographic characteristics as the active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days.
|
|---|---|---|
|
Cholesterol Ester Production Rate at Week 6
|
1.12 (mg/kg)/hr
Standard Deviation 0.24
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 6Population: FAS included all enrolled participants who had any measurement of cholesterol ester production rate available.
Blood level of LDL-C and total cholesterol (TC) was measured following a 12-hours fasting.
Outcome measures
| Measure |
Rheumatoid Arthritis Cohort
n=36 Participants
Active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days and then received CP-690,550 10 mg tablet orally twice daily for 6 weeks.
|
Healthy Volunteer Cohort
n=31 Participants
Healthy volunteers with similar baseline demographic characteristics as the active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days.
|
|---|---|---|
|
Low-density Lipoprotein Cholesterol (LDL-C) and Total Cholesterol Concentration
Baseline: LDL-C
|
124.61 mg/dL
Standard Deviation 28.55
|
144.88 mg/dL
Standard Deviation 36.36
|
|
Low-density Lipoprotein Cholesterol (LDL-C) and Total Cholesterol Concentration
Baseline: TC
|
193.79 mg/dL
Standard Deviation 32.56
|
221.57 mg/dL
Standard Deviation 42.12
|
|
Low-density Lipoprotein Cholesterol (LDL-C) and Total Cholesterol Concentration
Week 6: LDL-C
|
142.68 mg/dL
Standard Deviation 39.02
|
NA mg/dL
Standard Deviation NA
Data not available at this time point since as per analysis plan healthy volunteers were enrolled only for baseline assessment period.
|
|
Low-density Lipoprotein Cholesterol (LDL-C) and Total Cholesterol Concentration
Week 6: TC
|
219.83 mg/dL
Standard Deviation 41.33
|
NA mg/dL
Standard Deviation NA
Data not available at this time point since as per analysis plan healthy volunteers were enrolled only for baseline assessment period.
|
SECONDARY outcome
Timeframe: Baseline, Week 6Population: FAS included all enrolled participants who had any measurement of cholesterol ester production rate available. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
Cholesterol ester fractional catabolic rate were calculated using a 3-pool model with a simulation, analysis and modeling (SAAM II) program. Fractional catabolic rate was the percentage of cholesterol ester which was replaced, transferred or lost per unit of time.
Outcome measures
| Measure |
Rheumatoid Arthritis Cohort
n=34 Participants
Active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days and then received CP-690,550 10 mg tablet orally twice daily for 6 weeks.
|
Healthy Volunteer Cohort
n=31 Participants
Healthy volunteers with similar baseline demographic characteristics as the active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days.
|
|---|---|---|
|
Cholesterol Ester Fractional Catabolic Rate
Baseline
|
2.43 percentage ester per hour (%/hr)
Standard Deviation 0.39
|
2.17 percentage ester per hour (%/hr)
Standard Deviation 0.36
|
|
Cholesterol Ester Fractional Catabolic Rate
Week 6
|
2.23 percentage ester per hour (%/hr)
Standard Deviation 0.31
|
NA percentage ester per hour (%/hr)
Standard Deviation NA
Data not available at this time point since as per analysis plan healthy volunteers were enrolled only for baseline assessment period.
|
SECONDARY outcome
Timeframe: Baseline, Week 6Population: FAS included all enrolled participants who had any measurement of cholesterol ester production rate available. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
LDL-apoB production rate were calculated using a 3-pool model with a simulation, analysis and modeling (SAAM II) program.
Outcome measures
| Measure |
Rheumatoid Arthritis Cohort
n=32 Participants
Active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days and then received CP-690,550 10 mg tablet orally twice daily for 6 weeks.
|
Healthy Volunteer Cohort
n=30 Participants
Healthy volunteers with similar baseline demographic characteristics as the active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days.
|
|---|---|---|
|
Low-density Lipoprotein Associated With Apolipoprotein B (LDL-apoB) Production Rate
Baseline
|
0.49 (mg/kg)/hr
Standard Deviation 0.12
|
0.50 (mg/kg)/hr
Standard Deviation 0.13
|
|
Low-density Lipoprotein Associated With Apolipoprotein B (LDL-apoB) Production Rate
Week 6
|
0.52 (mg/kg)/hr
Standard Deviation 0.12
|
NA (mg/kg)/hr
Standard Deviation NA
Data not available at this time point since as per analysis plan healthy volunteers were enrolled only for baseline assessment period.
|
SECONDARY outcome
Timeframe: Baseline, Week 6Population: FAS included all enrolled participants who had any measurement of cholesterol ester production rate available. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
Fractional catabolic rate for LDL ApoB were calculated using the 13 carbon (13C) isotopic enrichment of very low density lipoprotein (VLDL) as the limiting value. Isotope 13C in plasma was measured using Gas Chromatography-Combustion-Isotope Ratio Mass Spectrometry (GC-C-IRMS).
Outcome measures
| Measure |
Rheumatoid Arthritis Cohort
n=32 Participants
Active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days and then received CP-690,550 10 mg tablet orally twice daily for 6 weeks.
|
Healthy Volunteer Cohort
n=30 Participants
Healthy volunteers with similar baseline demographic characteristics as the active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days.
|
|---|---|---|
|
Low-density Lipoprotein Associated With Apolipoprotein B (LDL-apoB) Fractional Catabolic Rate
Baseline
|
1.61 %/hr
Standard Deviation 0.37
|
1.50 %/hr
Standard Deviation 0.35
|
|
Low-density Lipoprotein Associated With Apolipoprotein B (LDL-apoB) Fractional Catabolic Rate
Week 6
|
1.57 %/hr
Standard Deviation 0.41
|
NA %/hr
Standard Deviation NA
Data not available at this time point since as per analysis plan healthy volunteers were enrolled only for baseline assessment period.
|
SECONDARY outcome
Timeframe: Baseline, Week 6Population: FAS included all enrolled participants who had any measurement of cholesterol ester production rate available. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
HDL-apoA1 production rate were calculated using a 3-pool model with a simulation, analysis and modeling (SAAM II) program.
Outcome measures
| Measure |
Rheumatoid Arthritis Cohort
n=32 Participants
Active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days and then received CP-690,550 10 mg tablet orally twice daily for 6 weeks.
|
Healthy Volunteer Cohort
n=30 Participants
Healthy volunteers with similar baseline demographic characteristics as the active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days.
|
|---|---|---|
|
High-density Lipoprotein Associated With Apolipoprotein A1 (HDL-apoA1) Production Rate
Baseline
|
0.57 mg/kg/hr
Standard Deviation 0.11
|
0.59 mg/kg/hr
Standard Deviation 0.16
|
|
High-density Lipoprotein Associated With Apolipoprotein A1 (HDL-apoA1) Production Rate
Week 6
|
0.65 mg/kg/hr
Standard Deviation 0.15
|
NA mg/kg/hr
Standard Deviation NA
Data not available at this time point since as per analysis plan healthy volunteers were enrolled only for baseline assessment period.
|
SECONDARY outcome
Timeframe: Baseline, Week 6Population: FAS included all enrolled participants who had any measurement of cholesterol ester production rate available. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
Fractional catabolic rate for HDL-apoA1 were calculated using the 13C isotopic enrichment of VLDL as the limiting value. Isotope 13C in plasma was measured using GC-C-IRMS.
Outcome measures
| Measure |
Rheumatoid Arthritis Cohort
n=32 Participants
Active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days and then received CP-690,550 10 mg tablet orally twice daily for 6 weeks.
|
Healthy Volunteer Cohort
n=30 Participants
Healthy volunteers with similar baseline demographic characteristics as the active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days.
|
|---|---|---|
|
High-density Lipoprotein Associated With Apolipoprotein A1 (HDL-apoA1) Fractional Catabolic Rate
Baseline
|
1.08 %/hr
Standard Deviation 0.22
|
1.02 %/hr
Standard Deviation 0.22
|
|
High-density Lipoprotein Associated With Apolipoprotein A1 (HDL-apoA1) Fractional Catabolic Rate
Week 6
|
1.11 %/hr
Standard Deviation 0.28
|
NA %/hr
Standard Deviation NA
Data not available at this time point since as per analysis plan healthy volunteers were enrolled only for baseline assessment period.
|
SECONDARY outcome
Timeframe: Baseline, Week 6Population: FAS included all enrolled participants who had any measurement of cholesterol ester production rate available. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
Cholesterol efflux rate was measured using isotope dilution method in which rate of appearance of isotope 13C-free cholesterol in plasma representing whole body efflux from tissues was assessed. Isotope 13C in plasma was measured using GC-C-IRMS.
Outcome measures
| Measure |
Rheumatoid Arthritis Cohort
n=34 Participants
Active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days and then received CP-690,550 10 mg tablet orally twice daily for 6 weeks.
|
Healthy Volunteer Cohort
n=31 Participants
Healthy volunteers with similar baseline demographic characteristics as the active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days.
|
|---|---|---|
|
Cholesterol Efflux Rate
Baseline
|
4.02 (mg/kg)/hr
Standard Deviation 0.96
|
4.35 (mg/kg)/hr
Standard Deviation 1.53
|
|
Cholesterol Efflux Rate
Week 6
|
4.04 (mg/kg)/hr
Standard Deviation 1.08
|
NA (mg/kg)/hr
Standard Deviation NA
Data not available at this time point since as per analysis plan healthy volunteers were enrolled only for baseline assessment period.
|
Adverse Events
Rheumatoid Arthritis Cohort
Healthy Volunteer Cohort
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Rheumatoid Arthritis Cohort
n=36 participants at risk
Active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days and then received CP-690,550 10 mg tablet orally twice daily for 6 weeks.
|
Healthy Volunteer Cohort
n=33 participants at risk
Healthy volunteers with similar baseline demographic characteristics as the active rheumatoid arthritis participants were assessed for baseline cholesterol flux kinetics for 3 days.
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal distension
|
5.6%
2/36
|
0.00%
0/33
|
|
Gastrointestinal disorders
Abdominal pain upper
|
2.8%
1/36
|
0.00%
0/33
|
|
Gastrointestinal disorders
Diarrhoea
|
2.8%
1/36
|
0.00%
0/33
|
|
Gastrointestinal disorders
Dyspepsia
|
5.6%
2/36
|
0.00%
0/33
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
2.8%
1/36
|
0.00%
0/33
|
|
Gastrointestinal disorders
Nausea
|
2.8%
1/36
|
0.00%
0/33
|
|
Gastrointestinal disorders
Toothache
|
2.8%
1/36
|
0.00%
0/33
|
|
Gastrointestinal disorders
Vomiting
|
2.8%
1/36
|
0.00%
0/33
|
|
General disorders
Irritability
|
2.8%
1/36
|
0.00%
0/33
|
|
General disorders
Oedema peripheral
|
2.8%
1/36
|
3.0%
1/33
|
|
Infections and infestations
Sinusitis
|
2.8%
1/36
|
0.00%
0/33
|
|
Infections and infestations
Upper respiratory tract infection
|
19.4%
7/36
|
0.00%
0/33
|
|
Infections and infestations
Urinary tract infection
|
8.3%
3/36
|
0.00%
0/33
|
|
Injury, poisoning and procedural complications
Epicondylitis
|
2.8%
1/36
|
0.00%
0/33
|
|
Injury, poisoning and procedural complications
Fall
|
2.8%
1/36
|
0.00%
0/33
|
|
Investigations
Blood pressure increased
|
2.8%
1/36
|
0.00%
0/33
|
|
Metabolism and nutrition disorders
Decreased appetite
|
2.8%
1/36
|
0.00%
0/33
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
2.8%
1/36
|
0.00%
0/33
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
2.8%
1/36
|
0.00%
0/33
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.8%
1/36
|
0.00%
0/33
|
|
Musculoskeletal and connective tissue disorders
Costochondritis
|
2.8%
1/36
|
0.00%
0/33
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
2.8%
1/36
|
0.00%
0/33
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
2.8%
1/36
|
0.00%
0/33
|
|
Nervous system disorders
Dizziness
|
2.8%
1/36
|
0.00%
0/33
|
|
Nervous system disorders
Headache
|
11.1%
4/36
|
12.1%
4/33
|
|
Nervous system disorders
Migraine
|
2.8%
1/36
|
3.0%
1/33
|
|
Nervous system disorders
Sciatica
|
2.8%
1/36
|
0.00%
0/33
|
|
Psychiatric disorders
Anxiety
|
2.8%
1/36
|
0.00%
0/33
|
|
Renal and urinary disorders
Dysuria
|
2.8%
1/36
|
0.00%
0/33
|
|
Renal and urinary disorders
Haematuria
|
2.8%
1/36
|
0.00%
0/33
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.8%
1/36
|
0.00%
0/33
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER